Synthesis of potential drug metabolites by a modified Udenfriend reaction

Tetrahedron Letters

Volumn 52, Issue 7, 2011, Pages 749-752

  Slavik, Roger ^a,b   Peters, Jens Uwe ^a   Giger, Rudolf ^a,c   Bürkler, Markus ^a   Bald, Eric ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

^b Steinbock Apotheke   (Switzerland)

^c GIGER MedChem Consulting   (Switzerland)

Author keywords

Aromatic hydroxylation; Biomimetic oxidation; Drug discovery; Metabolites

Indexed keywords

BUSPIRONE; CHLORPROMAZINE; CLOZAPINE; DILTIAZEM; DRUG METABOLITE; IMIPRAMINE; PROPRANOLOL;

ARTICLE; CHEMICAL REACTION; DRUG SYNTHESIS; HYDROXYLATION; IN VIVO STUDY; OXIDATION KINETICS; STRUCTURE ANALYSIS;

EID: 78651396664     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2010.12.014     Document Type: Article

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54. Black, tarry products were also observed in the attempted oxidation of propranolol under the original Udenfriend conditions, which gave no conversion of propranolol; thus, the observed polymeric products may originate at least in part from other components of the reaction system, for example, ascorbic acid.
55. We also attempted to minimize over-oxidation by using the described modified Udenfriend procedure, however with lower amounts (one third) of reagents, and a limited reaction time (2 h). Under these conditions, clozapine gave, after incomplete conversion, 1a in 1.5% yield (62% purity), and 1b in 1.0% yield (100% purity), whereas no oxidation was observed for propranolol.